From Vector Toxicity to Successful Clinical Evaluation: Highlights of the 2nd Annual Meeting of the British Society for Gene Therapy

Manchester was the setting for the second annual meeting of the British Society for Gene Therapy (BSGT). With an increase in BSGT membership, there was also a welcome increase in the number of delegates attending the conference, from 208 to 222, compared with the previous year. Recent advances in the field of gene therapy were presented and these spanned the development, use and refinement of a wide range of gene-delivery approaches using nonviral vectors and many types of viral vectors, including adenovirus, adenoassociated virus (AAV), lentivirus, Semliki Forest virus (SFV) and herpes simplex virus (HSV). This year, there was a particular focus on advances in cancer gene therapy and in-depth discussion on vector toxicity and safety, with particular regard to retroviral vectors. In addition, there were also sessions that focused on gene therapy for genetic disease, methods to improve gene delivery and expression as well as discussions on the use of stem cells in cellular therapy. One particular aim of the conference was to reinforce the need for high-quality, basic research in gene therapy to facilitate a successful translation into clinical studies. Evidence of this was provided at the conference with many encouraging results from clinical trials, principally in oncolytic gene therapy and in the use of gene therapy for the treatment of genetic disease. This report describes some of the highlights of the data presented. Vector toxicity & safety Recent adverse effects reported in clinical trials following viral-mediated gene transfer have resulted in the need for thorough safety evaluation of these types of vectors [1–3]. On the first full day of the conference, Mike Themis (Imperial College, London, UK) presented data on an in vivo fetal model to test the safety of lentivirus gene-therapy vectors that highlighted the potential oncogenic risks of lentiviral vectors. The fetal model is an attractive proposition: potentially it could provide early treatment for genetic disease, may allow stem-cell transfer for permanent correction, has immune tolerance for longterm gene expression and allows for the easy identification of any adverse effects of gene delivery such as developmental problems. Themis and colleagues have previously shown that in utero administration of several lentiviral vectors to day-16 mouse fetuses resulted in efficient vector spread and long-term gene expression. However, this talk focused on the high frequency of liver tumors observed after injection of third-generation lentiviral vectors based on equine infectious anemia virus (EIAV). In mice treated with these EIAV lentiviral vectors, originating from Oxford BioMedica Ltd (UK), tumors were detected, in some cases in eight out of ten mice, depending on the vector type. Multiple tumors were presented in some animals. It was concluded that the fetal model may now present itself as a useful